Primary biliary cirrhosis (PBC) is an organ-specific autoimmune liver disease characterized by progressive loss of intrahepatic small bile ducts. Cellular immune mechanisms involving T cell reaction are thought to be involved significantly in the pathogenesis of PBC. Recent studies have independently revealed enhanced T helper type 17 (Th17) response and ...

Autoimmunity may evolve in predisposed individuals following an exogenous trigger. Autoimmunity is affected by genetic, immune, hormonal, and environmental factors. Immune mechanisms in heart diseases are complex and often not completely understood. Several cardiac disorders are believed to be mediated by an immune reaction. Both humoral and cellular immunity are ...

Autoantibodies against various retinal proteins, including anti-carbonic anhydrase II (CAII) autoantibodies, have been found in patients with cancer-associated retinopathy and autoimmune retinopathy without diagnosed cancer. We studied sera from retinopathy patients that showed reactivity with a 30-kDa retinal protein, which was identified as carbonic anhydrase II (CAII), and immunolabeled cells ...

Although parasite-mediated host cell lysis is deemed to be an important cause of tissue destruction in ocular toxoplasmosis (OT), the severity of the disease is probably correlated with hypersensitivity and inflammation. Notwithstanding, the mechanisms that regulate the inflammatory process in recurrent OT are poorly understood. Recent evidence has identified interleukin ...

High Mobility Group Box 1 (HMGB1) is a nuclear protein participating in chromatin architecture and transcriptional regulation. Recently, there is increasing evidence that HMGB1 contributes to the pathogenesis of chronic inflammatory and autoimmune diseases due to its pro-inflammatory and immunostimulatory properties. Elevated expression of HMGB1 was found in the sera ...

Glaucomatous neurodegeneration has been associated with the activation of multiple pathogenic mechanisms that can result in RGC death and axonal degeneration. Growing evidence obtained from clinical and experimental studies over the last decade also strongly suggests the involvement of the immune system in the neurodegenerative process of glaucoma. The roles ...

4-1BB, a member of the tumor necrosis factor receptor (TNFR) family, binds the 4-1BB ligand (4-1BBL), works as a costimulatory molecule, and regulates T cell-mediated immune responses. Although inflammation is an essential pathological feature of myocarditis, the role of 4-1BB in experimental autoimmune myocarditis (EAM) remains unclear. Lewis rats were ...

Systemic lupus erythematosus is a multisystem autoimmune disease characterized by the production of numerous antinuclear autoantibodies and inflammatory mediators. The BXSB mouse strain is an excellent model of the disease. Previous work has determined a number of important disease susceptibility intervals that have been isolated in separate congenic strains. Here, ...

The cellular prion protein (PrP(C)) is widely expressed in neural and non-neural tissues, but its function is unknown. Elucidation of the part played by PrP(C) in adaptive immunity has been a particular conundrum: increased expression of cell surface PrP(C) has been documented during T-cell activation, yet the functional significance of ...

T regulatory cells (Treg cells) suppress immune responses to maintain self tolerance, but they also protect cancerous tissues. I propose a model to potentially unify the diverse functions of Treg cells. This assumes that Treg cells provide a complementary immunological arm to a physiological tissue-protecting mechanism, driven by low oxygen ...

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by dysregulated immune responses mediated by T and B cells. A tolerogenic peptide, designated hCDR1, ameliorated the serological and clinical manifestations of SLE in mouse models of lupus. We investigated the role of B-cell activating factor (BAFF) in the beneficial effects ...

Type 1 diabetes (T1D) is an organ-specific autoimmune disease resulting from the specific destruction of insulin-producing pancreatic beta-cells, culminating in a state of hypoinsulinemia and hyperglycemia. Pathogenesis of T1D comprises complex series of events from the initial sensitization of antigen-presenting cells (APCs) to beta-cell antigens to almost total insulin deficiency ...

Lipid peroxidation occurs frequently in patients with systemic autoimmune diseases and contributes to autoimmune vascular inflammation. Oxidized low-density lipoprotein (oxLDL) interacts with beta2-glycoprotein I (beta2GPI), forming oxLDL/beta2GPI complexes. Circulating oxLDL/beta2GPI complexes and autoantibodies to these complexes have been demonstrated in patients with systemic lupus erythematosus and antiphospholipid syndrome. These findings ...

Chlamydia trachomatis serovar D produces large quantities of HSP60-1 during infections, which accumulate inside the host cell inducing autoimmunity. We compare the aminoacid sequences of the human HSP60 with the bacterial counterpart to better elucidate how CTHSP60 may simulate HSP60 from human origin during infection and may induce an autoimmune ...

The basic understanding of inflammatory dermatoses and autoimmune-mediated skin disorders has greatly advanced and broadened our understanding of underlying immune mechanisms that shape the complex network of chronic inflammation and autoimmunity. The new treatment options for psoriasis exemplify how new insights into (auto)immune responses, especially the role and function of ...

Multi-organic failure in the context of autoimmune diseases is a multi-factorial condition where different pathways concur to produce a global system breakdown. Some of these pathways include the coagulation, fibrinolysis, kinin and complement cascades which in normal conditions work together to provide a comprehensive response to injury. In pathologic conditions ...

MicroRNAs (miRNAs)-mediated RNA interference are emerging as an important regulatory pathway for various biological processes, including development, differentiation, and homeostasis. Accumulated evidence suggests that miRNAs regulate T cell and B cell differentiation, proliferation, and apoptosis. Deletion of miRNAs in hematopoietic stem cells or in thymus disrupts T cell homeostasis and ...

The forkhead family transcription factor FOXP3 plays a fundamental role in immune homeostasis. FOXP3 dysfunction in regulatory T cells (Tregs) contributes to multiple disease processes such as autoimmunity, tumor development, and viral infection. FOXP3 cooperates and associates with a group of other transcriptional factors, co-repressors and co-activators in Tregs to ...

Interleukin 21 (IL-21) is a pleiotropic cytokine produced by CD4 T cells that affects the differentiation and function of T, B, and NK cells by binding to a receptor consisting of the common cytokine receptor gamma chain and the IL-21 receptor (IL-21R). IL-21, a product associated with IL-17-producing CD4 T ...

There have been significant advances in the treatment of SLE, which have produced major impacts on morbidity and in some cases mortality. The major drugs of the last three decades in treatment of SLE have been corticosteroids, AZA, MTX and cyclophosphamide. However, these drugs have considerable toxicities, and with the ...

OBJECTIVES: To review current developments, regarding the pathophysiologic role of monocytes and macrophages in systemic lupus erythematosus (SLE). METHODS: We searched Medline for articles written in the English language using the following terms: monocyte(s) or macrophage(s) and lupus. Although our search spanned the years 1971 to 2008, the majority of ...

Impaired functional activity of T regulatory cells has been reported in allergic patients and results in an increased susceptibility to autoimmune diseases. The master regulator of T regulatory cell differentiation, the transcription factor FOXP3, is required for both their development and function. Despite its key role, relatively little is known ...

MicroRNA (miRNA) control has emerged as a critical regulatory principle in the mammalian immune system. Genetic ablation of the miRNA machinery, as well as loss or deregulation of certain individual miRNAs, severely compromises immune development and response and can lead to immune disorders like autoimmunity and cancer. Although individual miRNAs ...

Systemic lupus erythematosus is a chronic, multisystemic, autoimmune disease that may involve the central, peripheral, and autonomic nervous systems and can present with a wide variety of neurological and psychiatric manifestations. In this article, we review the recent literature pertaining to the pathogenesis of neuropsychiatric systemic lupus erythematosus (NPSLE). We ...

Fas and Fas ligand (FasL), members of the tumor necrosis factor (TNF) and TNF-receptor (TNFR) families of molecules, are involved in apoptosis. They are expressed in membrane-associated as well as soluble forms (sFas, and sFasL). Apoptotic defects underlie some models of autoimmune diseases, and they have been proposed in the ...

The immune system is responsible for not only eliminating threats to the body, but also for protecting the body from its own immune responses that would cause harm if left unchecked. Forkhead box protein 3 (FOXP3) is a forkhead family member with an important role in the development and function ...

Our laboratory focuses on the study of the molecular regulation of T lymphocyte homeostasis, particularly as it relates to immunological tolerance, apoptosis, and autoimmune diseases. Through intense molecular research on the regulation of lymphocyte fate, the Fas receptor and other tumor necrosis factor receptors as well as their ligands have ...

Low-affinity Fcgamma receptors (FcgammaRs) mediate the effects of immunoglobulin G (IgG) antibodies on leukocytes, including recruitment to inflammatory lesions, phagocytosis, antibody-dependent cellular cytotoxicity, release of inflammatory mediators and regulation of B cell activation. These functions are an important part of the mammalian response to infection, but if deployed inappropriately can ...

Autoantibodies against particular nuclear components, such as chromatin and snRNPs, are a characteristic feature of the autoimmune disease systemic lupus erythematosus. The last decade, evidence has suggested that apoptotic cells are the main source of autoantigens in this disease. Therefore, it has been proposed that protein modifications occurring during apoptosis ...

The Transcription factor FoxP3 belongs to the forkhead/winged-helix family of transcriptional regulators and shares general structural features with other FoxP family members. FoxP3 functions as a master of transcription for the development of regulatory T-cells (Treg cells) both in humans and in mice. Natural genetic mutations ofFoxP3 that disrupt its ...

Histone deacetylase inhibitors are under investigation in the clinic as a new class of anti-cancer therapeutics. While recent studies have also suggested their potential as inhibitors of a wide spectrum of inflammatory reactions, the anti-inflammatory mechanism of action of these compounds is not fully defined. We show here that the ...

HMGB1, an evolutionarily conserved chromosomal protein, was recently re-discovered to act as a "danger signal" (alarmin) to alert the innate immune system for the initiation of host defense or tissue repair. Extracellular HMGB1 can be either passively released from damaged/necrotic cells or secreted by activated immune cells. Upon stimulation, dendritic ...

A Proliferation Inducing Ligand (APRIL) was first identified as a cytokine expressed predominantly by tumour tissues and was not found in most normal tissues. The activity of this new cytokine, in terms of its ability to stimulate tumour cell proliferation in vivo, determined the catchy acronym of yet another TNF ...

Autoimmune connective tissue diseases (ACTDs) constitute a heterogeneous group of chronic immune-mediated inflammatory disorders, primarily affecting connective tissues and usually characterized by multisystem involvement with variable and frequently overlapping clinical manifestations. Abnormal immune regulation patterns and persistent inflammation are ACTD hallmarks. In such a context, autoimmunity/inflammation-associated cellular and molecular networks ...

An autoimmune response to herniated nucleus pulposus has been proposed to constitute a pathophysiologic mechanism for inducing sciatica based on the fact that nucleus pulposus under normal conditions is excluded from the development of immunological tolerance. The manifestation of an autoimmune response comprises different steps starting with antigen capture, continuing ...

CD4+/FOXP3+ regulatory T-cells (Tregs) are essential for the maintenance of self-tolerance and Tregs deficiency results in spontaneous autoimmunity in both mice and humans. The forkhead box P3 (FOXP3) expression is required for both survival of Tregs precursors as well as their function. This suggests that Tregs may use multiple mechanisms ...

The CTLA-4 pathway is recognized as a major immune inhibitory axis and is a key therapeutic target for augmenting antitumor immunity or curbing autoimmunity. CTLA-4-deficient mice provide the archetypal example of dysregulated immune homeostasis, developing lethal lymphoproliferation with multiorgan inflammation. In this study, we show that surprisingly these mice have ...

Apoptosis is a programmed cell death that represents a normal component of the development, differentiation and health of multicellular organisms leading to an adequate cellular turnover and homeostasis. In autoimmune diseases, the immune system recognizes various autoantigens causing damage in target organs. Dead cells represent an important source of autoantigens ...

Autoimmune thyroid diseases (Hashimoto thyroiditis, Graves' disease, postpartum thyroiditis, atrophic thyroiditis and drug induced thyroiditis) are prevalent disorders worldwide, especially in women (related to the millieu of sex steroids and X chromosome effects on the thyroid and the immune system). Disruption of thyroid self tolerance, usually induced by an infection, ...

Recent evidences suggest that the apoptotic pathway plays a central role in tolerazing T cells to tissue-specific self antigen, and may drive the autoimmune phenomenon in the salivary glands. We found that retinoblastoma-associated protein RbAp48 overexpression induces p53-mediated apoptosis in the salivary glands caused by estrogen deficiency. We demonstrated that ...

Autoimmunity and the pathogenesis of autoimmune diseases were a major focus of the Walter and Eliza Hall Institute, where I started my research career. After my initial studies on immune cell culture and immune regulation, I returned to an analysis of the pathogenesis of human autoimmunity in London. Linking upregulated ...

Environmental and predisposing genetic factors are known to play a crucial role in the development of systemic autoimmune diseases. With respect to the role of environmental factors, it is not known how and to what extent they contribute to the initiation and exacerbation of systemic autoimmunity. In the present study, ...

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by B cell hyperactivity and defective T-cell function, with production of high titer autoantibodies. In the recent years, conceptual advances and the introduction of new therapies are yielding improvements in the management of this disease. In recent years, clinical studies have ...

For years, clusterin has been recognized as a secreted protein and a large number of works demonstrated that this ubiquitously expressed protein has multiple activities. Among the described activities several were related to inflammation and immunity such as its regulatory activity on complement. Then it became clear that a nuclear ...

Allergic diseases such as asthma, rhinitis and eczema are increasing in prevalence worldwide, in particular in industrialised countries affecting up to 20% of the population. Regulatory T-cells (Tregs) have been shown to be critical in T-cell homeostasis and in the maintenance of immune responses, such as prevention of autoimmunity and ...

INTRODUCTION: Lupus patients need alternatives to steroids and cytotoxic drugs. We recently found that apigenin, a non-mutagenic dietary flavonoid, can sensitize recurrently activated, normal human T cells to apoptosis by inhibiting nuclear factor-kappa-B (NF-kappaB)-regulated Bcl-xL, cyclooxygenase 2 (COX-2), and cellular FLICE-like inhibitory protein (c-FLIP) expression. Because sustained immune activation and ...

The mammalian eye is protected against pathogens and inflammation in a relatively immune-privileged environment. Stringent mechanisms are activated that regulate external injury, infection, and autoimmunity. The eye contains a variety of cells expressing vasoactive neuropeptides (VNs), and their receptors, located in the sclera, cornea, iris, ciliary body, ciliary process, and ...

BACKGROUND: CD4(+)CD25(+)FOXP3(+) Regulatory T cells (Treg) play a central role in the immune balance to prevent autoimmune disease. One outstanding question is how Tregs suppress effector immune responses in human. Experiments in mice demonstrated that Treg restrict effector T cell (Teff) responses by deprivation of the growth factor IL-2 through ...

Advances in genetics and new understanding of the molecular pathways that mediate innate and adaptive immune system activation, along with renewed focus on the role of the complement system as a mediator of inflammation, have stimulated elaboration of a scheme that might explain key mechanisms in the pathogenesis of systemic ...

Since their discovery in the 1950s interferons have been the scope of investigation in many diseases as therapeutic as well as pathogenetic factors. We know they have immune stimulatory and immune regulatory effects. This apparently counter-intuitive mechanism can be summarized as immunomodulatory action and seems to be very effective in ...